Abstract
Ovarian cancer (OC) is the leading cause of death from gynecological malignancy. However, the mechanism by which OC develops remains largely unknown. Increases in cytosolic free Ca2+ ([Ca2+]i) can result in different physiological changes including cell growth, differentiation and death. The transient receptor potential (TRP) C channels are nonselective cation channels with permeability to Ca2+. Here we report that TRPC3 channels promote human OC growth. The TRPC3 protein levels in human OC specimens were greatly increased than those in normal ovarian specimens. Downregulating TRPC3 expression in SKOV3 cells, a human OC cell line, led to reduction of proliferation, suppression in epidermal growth factor-induced Ca2+ influx, dephosphorylation of Cdc2 and CaMKIIα and prolonged progression through M phase of these cells. Further, decreased the expression of TRPC3 suppressed the tumor formation generated by injecting SKOV3 cells in nude mice. Together, our results suggest that increased activity of TRPC3 channels is necessary for the development of OCs.
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Acknowledgements
We thank Q Hu and HL Yao for technical support and B Shen for reading the article. This work was supported by grants from the 973 Program (2006CB806600), projects 30711120566, 30621062, U0632006 from the National Natural Science Foundation of China and project B117 from Shanghai Leading Academic Discipline Project.
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Yang, S., Cao, Q., Zhou, K. et al. Transient receptor potential channel C3 contributes to the progression of human ovarian cancer. Oncogene 28, 1320–1328 (2009). https://doi.org/10.1038/onc.2008.475
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DOI: https://doi.org/10.1038/onc.2008.475
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